M3258
Based on 5 publication(s) in Google Scholar
M3258 is an orally bioavailable, potent, reversible and highly selective immunoproteasome subunit LMP7 (β5i) inhibitor. M3258 exerts high biochemical (IC50=3.6 nM) and cellular (IC50=3.4 nM) potency against the LMP7 subunit. M3258 shows strong antitumor efficacy in multiple myeloma xenograft models. M3258 leads to a significant and prolonged suppression of tumor LMP7 activity and ubiquitinated protein turnover and the induction of apoptosis in multiple myeloma cells.
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- Pureza: 98.0%
- No. CAS: 2285330-15-4
- Fòrmula: C17H20BNO5
- Peso molecular:329.16
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Publications Citing Use of MedChemExpress (MCE) M3258
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Actividad biológica
LMP7[1]
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Hepatocyte | IC50 |
64 μM
Compound: 50
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Cytotoxicity against Wistar Han rat hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against Wistar Han rat hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
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[PMID: 34228444] |
| Hepatocyte | IC50 |
91 μM
Compound: 50
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Cytotoxicity against human primary hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against human primary hepatocytes assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
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[PMID: 34228444] |
| HepG2 | IC50 |
48 μM
Compound: 50
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Cytotoxicity against human HepG2 cells assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
Cytotoxicity against human HepG2 cells assessed as depletion of ATP content incubated for 48 to 72 hrs by CellTiter-Glo luminescent assay
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[PMID: 34228444] |
M3258 inhibits human LMP7 with a mean IC50 of 4.1 nM. M3258 displays weak activity against the constitutive proteasome subunit β5 (mean IC50=2519 nM). M3258 potently inhibits LMP7 in the human multiple myeloma cell lines MM.1S and U266B1 and in human, rat, and dog PBMCs with IC50s between 2 and 37 nM[2].
M3258 induces a >four fold accumulation of ubiquitinated proteins with an EC50 of 1980 nM in MM.1S cells. M3258 interferes with immunoproteasome function. M3258 also induces apoptosis assessed by caspase 3/7 activity (EC50=420 nM;>3.5-fold induction) and reduces MM.1S cell viability (IC50=367 nM)[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MM.1S cells
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Concentration:0.01-100 nM
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Incubation Time:2 hours
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Result:Potently inhibited LMP7 in the human multiple myeloma cell lines MM.1S (IC50=2.2 nM).
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female H2d Rag2 mice or female CB-17 SCID mice (U266B1 subcutaneous xenograft model; MM.1S subcutaneous xenograft model)[2]
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Dosage:1 mg/kg in U266B1 subcutaneous xenograft model; 10 mg/kg in MM.1S subcutaneous xenograft model
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Administration:P.o.; either once daily, every 2 days or twice weekly (days 1 and 4)
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Result:Displayed significant and strong antitumor efficacy.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 2285330-15-4
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Appearance Solid
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Peso molecular 329.16
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Fòrmula C17H20BNO5
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Color White to off-white
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SMILES
O=C(N[C@@H](CC1=COC2=C1C=CC=C2)B(O)O)[C@H]3[C@@H]4CC[C@@H](O4)C3
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (5)
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Journal Impact Factor
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Most Recent
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Cell Death Dis
Targeting RNA polymerase I to boost natural killer cell anticancer activity in multiple myeloma. [Abstract]2025 Nov 28;16(1):865. PMID: 41315184 -
Cell Death Dis
Inhibition of p38 MAPK or immunoproteasome overcomes resistance of chronic lymphocytic leukemia cells to Bcl-2 antagonist venetoclax. [Abstract]2022 Oct 8;13(10):860. PMID: 36209148 -
Proc Natl Acad Sci U S A
2025 Nov 25;122(47):e2518190122. PMID: 41264257 -
J Med Chem
α-Aminoboronic Acid Moieties in Boro Dipeptides Modulate Proteasome Subunit Selectivity and Provide Access to Compounds with Potent Anticancer and Anti-Inflammatory Activity. [Abstract]2025 Dec 25;68(24):26405-26417. PMID: 41344819 -
Sci Rep
Highly specific Immunoproteasome inhibitor M3258 induces proteotoxic stress and apoptosis in KMT2A::AFF1 driven acute lymphoblastic leukemia. [Abstract]2025 May 19;15(1):17284. PMID: 40389585
Solvente y solubilidad
DMSO : 250 mg/mL (759.51 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (6.32 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (6.32 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (285 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Klein M, et al. Structure-Based Optimization and Discovery of M3258, a Specific Inhibitor of the Immunoproteasome Subunit LMP7 (β5i) [published online ahead of print, 2021 Jul 6]. J Med Chem. 2021;10.1021/acs.jmedchem.1c00604. [Content Brief]
[2]. Sanderson MP, et al. M3258 Is a Selective Inhibitor of the Immunoproteasome Subunit LMP7 (β5i) Delivering Efficacy in Multiple Myeloma Models [published online ahead of print, 2021 May 27]. Mol Cancer Ther. 2021;10.1158/1535-7163.MCT-21-0005. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 3.0380 mL | 15.1902 mL | 30.3804 mL | 75.9509 mL |
| 5 mM | 0.6076 mL | 3.0380 mL | 6.0761 mL | 15.1902 mL | |
| 10 mM | 0.3038 mL | 1.5190 mL | 3.0380 mL | 7.5951 mL | |
| 15 mM | 0.2025 mL | 1.0127 mL | 2.0254 mL | 5.0634 mL | |
| 20 mM | 0.1519 mL | 0.7595 mL | 1.5190 mL | 3.7975 mL | |
| 25 mM | 0.1215 mL | 0.6076 mL | 1.2152 mL | 3.0380 mL | |
| 30 mM | 0.1013 mL | 0.5063 mL | 1.0127 mL | 2.5317 mL | |
| 40 mM | 0.0760 mL | 0.3798 mL | 0.7595 mL | 1.8988 mL | |
| 50 mM | 0.0608 mL | 0.3038 mL | 0.6076 mL | 1.5190 mL | |
| 60 mM | 0.0506 mL | 0.2532 mL | 0.5063 mL | 1.2658 mL | |
| 80 mM | 0.0380 mL | 0.1899 mL | 0.3798 mL | 0.9494 mL | |
| 100 mM | 0.0304 mL | 0.1519 mL | 0.3038 mL | 0.7595 mL |
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